From Preserved, to Preservative-free Cyclosporine 0.1% Enhanced Triple Glaucoma Therapy

Changing From Preserved, to Preservative-free Cyclosporine 0.1% Enhanced Triple Glaucoma Therapy: Impact on the Rate and Severity of Ocular Surface Disease

There is a lack of evidence on the impact of switching from a combined preserved anti-glaucoma regimen to a preservative-free (PF) one, while employing sufficiently robust OSD metrics. The investigators have therefore carried out a single center, prospective, crossover investigation to compare the 6-month effect of switching well controlled open-angle glaucoma patients with at least moderate glaucoma therapy-related ocular surface disease from preserved to triple preservative-free therapy with and without cyclosporine 0.1% dosed in the evening.

Study Overview

• Status: Completed
• Conditions: Glaucoma; Ocular Surface Disease
• Intervention / Treatment: Diagnostic test: Assessment of ocular surface staining (Oxford score 0-15 scale); Drug: mean diurnal intraocular pressure-lowering

Detailed Description

Halting and reversing glaucoma therapy-related ocular surface disease (GTR-OSD) will improve the success of long-term medical therapy, impacting millions of patients worldwide. Chronic medical therapy for glaucoma may be immensely benefitted by limiting disabling GTR-OSD, which would aid in the prevention of blindness. In 2015 a novel cationic formulation of cyclosporine A 0.1% was approved with once in the evening dosing in Europe. It is an effective, targeted immunomodulatory compound reducing inflammatory mediators and providing healing of the ocular epithelium. There remains however a paucity of published controlled evidence for GTR-OSD patients treated with this formulation. In addition, there is a lack of evidence on the impact of switching from a combined preserved anti-glaucoma regimen, to a preservative-free one, while employing sufficiently robust OSD metrics. The investigators have therefore carried out a single center prospective, crossover investigation to compare the 6-month effect of switching well controlled open-angle glaucoma patients with at least moderate GTR-OSD, from preserved to triple PF therapy with and without PF cyclosporine 0.1% dosed in the evening.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Thessaloniki, Greece, 55536
    • University Department of Ophthalmology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

• Adult patients with well controlled open-angle glaucoma
• Patients chronically treated for more than 6 months with preserved, branded, or generic, triple antiglaucoma therapy comprising latanoprost and dorzolamide/timolol fixed combination
• Subjects should have experienced at least 1 symptom of dry eye (soreness, scratchiness, dryness, grittiness, and burning)
• Additionally, patients should demonstrate at least one of the objective signs for OSD at baseline: positive conjunctival staining with lissamine green and/or evidence of positive corneal staining with fluorescein (assessed with the 15-point Oxford scale),
• Patients must show a BUT<8 seconds
• On screening patients should show a Schirmer test without anesthesia (Schirmer-I test) ≥3 and ≤10 mm in 5 minutes.
• When both eyes qualify the worse eye will be included in the study.

Exclusion criteria

• Best corrected visual acuity <1/10
• Patients with severe dry eye disease or Sjogren's disease
• Presence of eyelid abnormality, corneal disorder or abnormality, ocular surface metaplasia, filamentous keratitis, or corneal neovascularization
• Patients who have undergone ocular surgery (of any type, including laser surgery), or ocular trauma within 4 months prior to screening
• Subjects who had punctal occlusion, or diathermy within 3 months prior to screening or abnormality of the nasolacrimal drainage apparatus.
• Known allergy, or sensitivity to any of the study medications
• Uncontrolled systemic disease, or history or active signs of ocular trauma, infection, inflammation, allergic disease, or herpes; corneal ulcers; recurrent erosions; or uveitis
• Female patients will be excluded if they are pregnant, breastfeeding, planning a pregnancy, or are unwilling to use a reliable form of contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Triple preservative-free therapy with placebo in the evening; In this arm subjects will be randomized to topical therapy comprising preservative-free tafluprost drops dosed in the evening (20:30) and dorzolamide/timolol fixed combination drops administered twice daily (8:00 and 20:00). Patients will use placebo (artificial tears) in the evening (21:00) for 6 months. At the end of this period patients will be crossed over to the other therapy (cyclosporine 0.1% in the evening)	Diagnostic test: Assessment of ocular surface staining (Oxford score 0-15 scale); Corneal and conjunctiva staining will be recorded according to the Oxford grading scheme for ocular staining (0-15 score).; Drug: mean diurnal intraocular pressure-lowering; At the end of each 6-month period patients will undergo diurnal intraocular pressure assessment with both therapies.
Active Comparator: Triple preservative-free therapy with cyclosporine 0.1% in the evening; In this arm subjects will be randomized to topical therapy comprising preservative-free tafluprost drops dosed in the evening (20:30) and dorzolamide/timolol fixed combination drops administered twice daily (8:00 and 20:00). Patients will use cyclosporine 0.1% drops in the evening (21:00) for 6 months. At the end of this period all patients will be crossed over to the other therapy (placebo in the evening)	Diagnostic test: Assessment of ocular surface staining (Oxford score 0-15 scale); Corneal and conjunctiva staining will be recorded according to the Oxford grading scheme for ocular staining (0-15 score).; Drug: mean diurnal intraocular pressure-lowering; At the end of each 6-month period patients will undergo diurnal intraocular pressure assessment with both therapies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in ocular staining (Oxford score)	The primary efficacy endpoint for this crossover study will be the mean change from baseline in the total ocular staining score as determined by the 15-point Oxford scale of staining on the study eye.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean diurnal IOP	Mean diurnal intraocular pressure with the two preservative-free therapies versus preserved baseline will be evaluated as secondary endpoint.	6 months
Osmolarity	Mean tear osmolarity with the two PF therapies versus preserved baseline will be evaluated as secondary endpoint.	6-months
Matrix-metalloproteinase-9 (MMP-9) over-expression	Mean MMP-9 over-expression with the two PF therapies versus preserved baseline will be evaluated as secondary endpoint.	6 months

Collaborators and Investigators

• Sponsor: Aristotle University Of Thessaloniki
• Investigators: Study Director: Andreas Katsanos, MD, PhD, University of Ioannina

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2018
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): June 29, 2020

Study Registration Dates

• First Submitted: December 11, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma
• Other Study ID Numbers: 399

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No